Gene expression is reduced in trans by inosine-containing dsRNA

Inosine residues may be introduced into long dsRNA (double-stranded RNA) molecules by the action of a family of editing enzymes, ADARs (adenosine deaminases that act on RNA). Furthermore, hyperediting of dsRNA by ADARs may result in up to 50% of adenosine residues being converted into inosine. While the effect of hyperediting has traditionally been thought to be limited to the edited dsRNA, we have recently shown that hyperedited dsRNA [I-dsRNA (inosine-containing dsRNA)] is able to down-regulate the expression of both reporter and endogenous mRNAs in cells, in trans. Down-regulation by I-dsRNA occurs both by reducing mRNA levels and by inhibiting of translation. This finding has important functional consequences for hyperediting by ADARs.